Exercise training is a safe and efficacious intervention for breast cancer patients following the completion of primary therapy (i.e., chemotherapy and radiation). In contrast, the role of exercise during primary BC therapy is less well accepted. Indeed, a perception exists that the conduct of scientifically rigorous exercise trials may not be possible during therapy due to poor adherence and attrition rates, elevated risk of adverse events, and significant patient selection bias. Nevertheless, a growing number of studies indicate that exercise is an effective therapy to mitigate certain cancer-related toxicities (e.g., deconditioning, fatigue) with adherence and attrition rates well within conventionally accepted levels, and with minimal AEs. Although the acceptance of exercise during therapy has made significant strides over the past decade, the prevailing dogma is still that exercise should be avoided during primary therapy. We propose a four-arm RCT to compare the effects and safety of supervised aerobic training performed during, after, or during and after (i.e., continuous AT) standard primary therapy, relative to attention-control, in 160 (n=40/group) early-stage BC patients. This grant has the following objectives: Primary aims: (1) To compare the difference in cardiorespiratory fitness between aerobic training and control during therapy versus aerobic training and control after therapy, (2) To compare the difference in oxygen transport organs that govern the aerobic training - fitness relationship, and (3) to compare the difference in patient-reported outcomes, adverse events, adherence, and attrition rates between study groups. A secondary aim is to compare the effect of continuous aerobic training, relative to all other groups, on primary aims 1 - 3. PUBLIC HEALTH RELEVANCE: The past decade has witnessed a dramatic increase in clinical and research interest in the application of exercise following a diagnosis of early breast cancer. Despite the growing evidence base, oncology professionals and patients remain skeptical of the safety, tolerability, and efficacy of aerobic training during primary therapy. Avoiding exercise during therapy may, however, have devastating acute as well as late- occurring consequences. There is a strong need to identify the optimal timing in which to initiate AT that maximizes the safety and tolerability of exercise whilst producing the most favorable improvements in cardiorespiratory fitness and other pertinent outcomes following a diagnosis of early breast cancer. This project will compare the effects and safety of aerobic training performed during, after, or during and after (i.e., continuous aerobic training) standard primary therapy, relative t control, in 160 (n=40/group) early-stage breast cancer patients.